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Inflammatory response of endothelial cells to a human endogenous retrovirus associated with multiple sclerosis is mediated by TLR4.

Duperray, Alain; Barbe, Delphin; Raguenez, Gilda; Weksler, Babette B.; Romero, Ignacio A.; Couraud, Pierre-Olivier; Perron, Hervé and Marche, Patrice N. (2015). Inflammatory response of endothelial cells to a human endogenous retrovirus associated with multiple sclerosis is mediated by TLR4. International Immunology, 27(11) pp. 545–553.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1093/intimm/dxv025
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Abstract

The MSRV (multiple sclerosis-associated retrovirus) belongs to the human endogenous retrovirus HERV-W family. The envelope protein originating from the MSRV has been found in most patients with multiple sclerosis (MS). This protein (Env-ms) has pro-inflammatory properties for several types of immune cells and could therefore play a role in MS pathogenesis by promoting the leukocyte diapedesis observed in the central nervous system of patients. Our study aims to analyze the effects of Env-ms on the blood-brain barrier (BBB) at a molecular and functional level. We demonstrate that the recombinant MSRV envelope is able to stimulate several inflammatory parameters in a human BBB in vitro model, the HCMEC/D3 brain endothelial cell line. Indeed, Env-ms induces over-expression of ICAM-1, a major mediator of leukocyte adhesion to endothelial cells, in a dose-dependent manner as well as a strong dose-dependent production of the pro-inflammatory cytokines IL-6 and IL-8. Furthermore, using a silencing approach with siRNAs, we show that Env-ms is recognized via the Toll-like receptor 4 receptor, a pattern recognition receptor of innate immunity present on endothelial cells. We also show, using functional assays, that treatment of brain endothelial cells with Env-ms significantly stimulated the adhesion and the transmigration of activated immune cells through a monolayer of endothelial cells. These findings support the hypothesis that MSRV could be involved in the pathogenesis of MS disease or at least in maintenance of inflammatory conditions, thus fueling the auto-immune disorder. MSRV could also play a role in other chronic inflammatory diseases.

Item Type: Journal Item
Copyright Holders: 2015 The Authors
ISSN: 1460-2377
Keywords: blood-brain barrier; leukocyte adhesion; autoimmune disease; retroviral envelope
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 44657
Depositing User: Ignacio A Romero
Date Deposited: 22 Oct 2015 08:39
Last Modified: 17 May 2017 21:30
URI: http://oro.open.ac.uk/id/eprint/44657
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